Low-molecular-weight fucoidan inhibits the proliferation of melanoma via Bcl-2 phosphorylation and PTEN/AKT pathway

Fucoidan, a sulfate polysaccharide obtained from brown seaweed, has various bioactive properties, including anti-inflammatory, anti -cancer, anti -viral, anti -oxidant, anti -coagulant, anti -thrombotic, anti-angiogenic, and antiHelicobacter pylori properties. However, the effects of low -molecular -weight fucoidan (LMW-F) on melanoma cell lines and three dimensional (3D) cell culture models are not well understood. This study aimed to investigate the effects of LMW-F on A375 human melanoma cells and cryopreserved biospecimens derived from patients with advanced melanoma. Ultrasonic wave was used to fragment fucoidan derived from Fucus vesiculosus into smaller LMW-F. MTT and live/dead assays showed that LMW-F inhibited cell proliferation in both A375 cells and patientderived melanoma explants in a 3D -printed collagen scaffold. The PTEN/AKT pathway was found to be involved in the anti -melanoma effects of fucoidan. Western blot analysis revealed that LMW-F reduced the phosphorylation of Bcl-2 at Thr 56, which was associated with the prevention of anti-apoptotic activity of cancer cells. Our findings suggested that LMW-F could enhance anti -melanoma chemotherapy and improve the outcomes of patients with melanoma resistance.